1. Field of the Invention
This invention relates to analyte sensors such as glucose sensors used in the management of diabetes and materials for making such sensors, for example comb-copolymeric membrane materials.
2. Description of Related Art
Analyte sensors such as biosensors include devices that use biological elements to convert a chemical analyte in a matrix into a detectable signal. There are many types of biosensors used for a wide variety of analytes. The most studied type of biosensor is the amperometric glucose sensor, which is crucial to the successful glucose level control for diabetes.
A typical glucose sensor works according to the following chemical reactions:
The glucose oxidase is used to catalyze the reaction between glucose and oxygen to yield gluconic acid and hydrogen peroxide (equation 1). The H2O2 reacts electrochemically as shown in equation 2, and the current is measured by a potentiostat.
A key problem in the use of this type of glucose sensor in the body is that the oxygen concentration in human body is too low compared with glucose concentration. Several approaches to solve this problem have been attempted in the past. The simplest way is to make a porous membrane from a fully oxygen permeable material. However, the small amount of enzyme disposed for glucose tends to become inactivated (see, e.g. U.S. Pat. No. 4,484,987, the contents of which are incorporated by reference). Another approach is to make homogenous polymer membrane with hydrophobic and hydrophilic regions leading to limited control of oxygen and glucose permeability (see, e.g. U.S. Pat. Nos. 5,428,123; 5,322,063, 5,476,094, the contents of which are incorporated by reference).
A key to stable and high sensitivity enzyme biosensors is that the sensor output must be limited only by the analyte of interest, not by any co-substrates or kinetically controlled parameters such as diffusion. In order to maximize the output current of biosensor, oxygen diffusion should be as high as possible while maintaining oxygen excess at the reaction surface. Silicone has the highest permeability to oxygen of any polymeric materials, but it is useless to directly use it as a membrane for glucose sensor because it is completely impermeable to glucose. Van Antwerp et al. have successfully developed linear random polyurea membranes with silicone hydrophobic component offering high oxygen permeability and with hydrophilic component offering limited glucose permeability (see e.g. U.S. Pat. Nos. 5,777,060, 5,882,494 and 6,642,015 B2). However, only polyethylene glycol (PEG) containing hydrophilic materials were considered optimal constituents for such membranes.